PRED2: Effect of the SCL16A11 Risk Haplotype on Treatments to Prevent Type 2 Diabetes

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Other)

Overall Status

Recruiting

CT.gov ID

NCT05990205

Collaborator

(none)

437

Enrollment

Location

Arms

73.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this randomized clinical trial is to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D in Mexican mestizos with prediabetes. The main question[s] it aims to answer are:

Evaluate the effect of the risk haplotype on weigth loss >3%
Evualuate the differences in lipid profiles and glycemic parameters (fasting glucose, HbA1c).

Participants will be randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day).

Researchers will compare carriers and non carriers of the risk haplotype of SLC16A11 to see if there are diferent treatment responses.

Condition or Disease	Intervention/Treatment	Phase
PreDiabetes	Drug: Life Style Intervention + Metformin Behavioral: Life Style Intervention	Phase 2

Detailed Description

Objectives: Dietary modification and/or metformin remain the most cost-effective treatment to prevent type 2 diabetes (T2D). Yet, there is an important variation in receiving the benefit among individuals. A haplotype in SLC16A11 is associated with decreased insulin action and risk for T2D in Mexicans. We aim to determine the impact of the risk haplotype on SLC16A11 on early therapeutic responses in treatments to prevent T2D.

Methods: We recrute individuals with at least one prediabetes criteria according to the American Diabetes Association with a body mass index (BMI) between 25 and 45 kg/m2. Participants are randomized into two groups: lifestyle intervention (LSI): hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week), or LSI + MET (750 mg metformin twice a day). Standardized dietitians delivere the LSI. The treatment goal is to achieve >3% weight loss during the 12-week follow-up. Participants are genotyped for the risk allele rs13342232 and rs75493593. The effects of the risk haplotype are evaluated with linear and logistic regressions adjusted by age, sex, five genetic principal components, BMI, and prediabetes criteria at baseline. Primary outcome is a significant interaction between the treatment arm and genotype in weight loss goal >3% after the treatment. Secondary outcome are differences in lipid levels and third outcome is differences in glycemic parameters (fasting glucose, HbA1c).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

437 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Effect of the Genetic Variants Typical of the Mestizo Population That Confer Risk of Having Metabolic Diseases on the Response to Common Treatments (Diet, Physical Activity, Metformin, Exercise).

Actual Study Start Date :

Apr 17, 2018

Anticipated Primary Completion Date :

Dec 20, 2023

Anticipated Study Completion Date :

May 25, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Life Style Intervention Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week)	Behavioral: Life Style Intervention hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week) Other Names: LSI
Active Comparator: Life Style Intervention + Metformin Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week) + (750 mg metformin twice a day).	Drug: Life Style Intervention + Metformin hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week) + Metformin extended release 750mg each 12 hours Other Names: LSI + MET

Arm

Intervention/Treatment

Active Comparator: Life Style Intervention

Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week)

Behavioral: Life Style Intervention

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week)

Other Names:

LSI

Active Comparator: Life Style Intervention + Metformin

Hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week) + (750 mg metformin twice a day).

Drug: Life Style Intervention + Metformin

hypocaloric diet, 25 kcal/kg of ideal weight, 45% of the total intake of carbohydrates, 30% lipids, and 25% protein sources + physical activity (>150 min medium intensity per week) + Metformin extended release 750mg each 12 hours

Other Names:

LSI + MET

Outcome Measures

Primary Outcome Measures

Change in weigth loss [12 weeks]
Number of participants in each treatment arm reaching the the goal weight loss >3%

Secondary Outcome Measures

Change in Total-Cholesterol parameters [12 weeks]
Decreasing concentration of Total-Cholesterol (mg/dl)
Change in LDL-Cholesterol parameters [12 weeks]
Decreasing LDL-Cholesterol levels (mg/dl)
Change in ApoB [12 weeks]
Decreasing ApoB levels (mg/dl)
Change in NonHDL-Cholesterol [12 weeks]
Decreasin NonHDL-Cholesterol levels (mg/dl)
Change in fasting glucose [12 weeks]
Decreasing fasting glucose levels (mg/dl)
Change in HbA1c [12 weeks]
Decreasin HbA1c levels (%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Mexican mestizos
At least one prediabetes criteria according to the American Diabetes Association: fasting glucose between 100-124 mg/dL, Glycosylated hemoglobin (HbA1c) between 5.7-6.4, and 2-hour blood sugar between 140 mg/dl-199 mg/dl after an oral load of 75g of glucose) (1);
Age ranged between 18-65 years
Overweight or obesity (BMI between 25.0 - 40 kg/m2).